United States: what's all this about eye drops contaminated with a superbug?

Over-the-counter eye drops contaminated with a never-before-seen superbug in the US: the death toll from the EzriCare Artificial Tearsoutbreak has risen to 4, with 14 cases of blindness and 81 people infected in 18 states of America.

Four deaths, fourteen people who lost their sight, four eyeballs surgically removed, all because of an over-the-counter eye drop designed to relieve dry eyes and available without a prescription. This story dates back to 2023 (the products were withdrawn from the market and the FDA alert was triggered in February 2023). It deserves to be told and shared with as many people as possible. Indeed, the mechanism that made this disaster possible is still unresolved.

The Centers for Disease Control and Prevention(CDC) has accurately reconstructed the scale of the outbreak: as of May 15, 2023, 81 patients had been identified in 18 U.S. states. All were infected by a strain of Pseudomonas aeruginosa known as VIM-GES-CRPA, an acronym that stands for carbapenem resistance so widespread as to make the bacteria virtually untreatable with most available antibiotics. Prior to this outbreak, this particular strain had never been reported in the United States.

The bacteria, the product, the manufacturer

Infections were not limited to the eyes. The CDC detected cases involving the respiratory tract, blood and other parts of the body, with a significant number of patients identified through surveillance sampling on hospital wards. The common point of contact, highlighted by epidemiological investigation and laboratory analysis, was EzriCare Artificial Tears and Delsam Pharma Artificial Tears, both manufactured and produced by Global Pharma Healthcare Private Limited, based in Chennai, India.

The Food and Drug Administration (FDA) had already issued an alert on February 2, 2023, calling on consumers and healthcare professionals to stop using EzriCare products immediately. The voluntary recall by Global Pharma was recommended by the FDA after finding violations of good manufacturing practices, such as the absence of adequate microbiological testing, single- or multi-dose vials lacking sufficient preservatives, and insufficient controls on tamper-evident packaging. The FDA subsequently placed the company under an "import alert", blocking the entry of its products into the U.S.

The CDC found the VIM-GES-CRPA strain inside previously opened EzriCare vials, collected from patients with and without eye infections, in two different states. Tests on unopened vials, carried out by the FDA, also revealed bacterial contamination.

Resistant to almost everything

In clinical terms, the CDC's data on the antibiotic resistance of this strain leaves little room for optimism. The isolates analyzed showed no susceptibility to cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, fluoroquinolones, polymyxins, amikacin, gentamicin and tobramycin. A list that covers most of the standard antibiotic arsenal. Only a subset of isolates showed sensitivity to cefiderocol, a latest-generation antibiotic.

This information, recently relayed online, is based on data dating back to May 15, 2023. The products mentioned have therefore already been withdrawn from the market, and the FDA alert has been active since February of the same year. This case does not describe an ongoing emergency, but a textbook case. It provides a better understanding of certain scenarios in which controls over the supply chain of imported OTC drugs are lacking, and lead to the problems described above.